1. FMT:Delivery Systems and Methodologies
Alexander Khoruts, MD
University of Minnesota
2014 James W. Freston Single Topic Conference

2. Disclosures Research Funding
CIPAC Limited: Research Grant Support for Preparation of Standardized Fecal Microbiota
NIH
University of Minnesota

3. Current Delivery Methods
Enema
Nasogastric Tube
Nasoduodenal Tube
Flexible sigmoidoscopy
Colonoscopy
Upper endoscopy

4. Dr. Ben Eiseman ( )
“In the early days of oral antibiotics we were plagued by frequent diarrhea in our patients due presumably to killing off intestinal bacteria. I was Chief of Surgery at the VA and simplistically considered merely reintroducing normal organisms to counter such absence. Those were days when if one had an idea, we simply tried it. It seemed to work and I wrote it up. It made a small splash…Best wishes. Ben Eiseman, Emeritus Professor of Surgery — Now age 93.” (Sept. 20, 2011)

5. Enema
Sample Protocol: Retention enema (may use a rectal balloon). Start in the left lateral decubitus position. Administer 60 mL q15 minutes x 4. Infuse slowly over 5 minutes, and ask the patient to rotate slowly over 10 minutes to right lateral decubitus position. Repeat.
No need for sedation
No need for endoscopist
Poor anal sphincter tone may be problematic
No diagnostic information regarding possible underlying bowel disease
Uncertain delivery of material quantity
Multiple administrations may be required
Nursing personnel, room, facility fees, lack of reimbursement

6. Nasogastric/Nasoduodenal Infusion
500 mL of fecal suspension administered via nasoduodenal tube at a rate of 50 mL/2-3 minutes

7. Nasogastric/Nasoduodenal Infusion
Radiologic procedure/fees associated with nasoduodenal tube placement
Vomiting and aspiration is a potential risk associated with NG administration. Consider excluding patients with gastroparesis, large hiatal hernia, reflux disease
Small bowel response to large quantities of fecal microbiota are unknown, but the procedure generally appears to be well-tolerated
Viability of donor microbiota following exposure to stomach acid and the digestive small bowel environment is unknown

8. Endoscopic Administration:
Colonoscopy, Flexible Sigmoidoscopy, (Upper Endoscopy)
Relatively simple within the US infrastructure with available endoscopic expertise
Diagnostic information regarding underlying disease
Certainty of delivery

9. Preparation Antibiotics regiment
Purging of the GI tract prior to the procedure

10. Fecal Microbiota Transplant
Katie Scott, New York Times, 2013

11. Beginnings…

12. UMN Microbiota Therapeutics Program
Donor Recruitment
Donor Screening
Donor
Laboratory Testing
Donation
Manufacturing
Laboratory/
Manufacturing
Cryopreservation
Release

13. UMN Microbiota Therapeutics Program
Rigorous Donor Screening and Testing
GMP Manufacturing
Antibiotic usage within 6 months
Infectious disease testing monthly (enteric and blood-borne)
Metabolic Syndrome
Autoimmunity
Allergic/atopic disease
Malnutrition
Neurologic and neurodevelopmental disorders
Clean, inspected facility
Consistent Manufacturing Protocol
Standardized Dosing (number of bacteria, etc.)
Cryopreservation
Tracking each unit
Malnutrition
Release criteria based on donor testing and manufacturing standards

15. Full-Spectrum MicrobiotaTM versus Defined Microbiota
Petrof, E. and Khoruts, A. Gastroenterology 2014

17. Recipient Microbiota
R-CDI
IBD
IBS
NASH
Autism
Diabetes

18. UMN Microbiota Therapeutics Program
Michael J. Sadowsky
Matthew Hamilton
Alexa Weingarden
JT Kang
Aleh Bobr
Carolyn Graiziger
Amanda Kabage